Respiratory mucous glycoprotein (MGP) is an essential secretion of airways. The control of these secretions has important implications for many disease states since too much or too little MGP can be associated with disease. Dexamethasone is often administered to patients with pulmonary disorders: its effects on MGP have not been clearly delineated. The effect of Dexamethasone on feline respiratory mucous glycoprotein (MGP) secretion in vitro, and Dexamethasone's effect correlated with the production of lipomodulin and with the inhibition of production of arachidonic acid metabolites. Dexamethasone caused a dose-dependent, reversible inhibition of MGP secretion, as well as up to a 220% increase in tissue lipomodulin content. This increase in lipomodulin content was associated with a marked reduction in the formation of the arachidonic acid metabolite PGE2. The addition of a mouse monoclonal antibody against lipomodulin completely blocked the Dexamethasone induced suppression of MGP secretion. These studies indicate that Dexamethasone inhibits MGP secretion from airways and that this effect is mediated by the induction of lipomodulin formation.